Instituto Carlos Chagas, Fiocruz Parana, Curitiba, Parana, Brazil.
Sci Data. 2021 Mar 25;8(1):93. doi: 10.1038/s41597-021-00818-w.
In humans and other eukaryotes, histone post-translational modifications (hPTMs) play an essential role in the epigenetic control of gene expression. In trypanosomatid parasites, conversely, gene regulation occurs mainly at the post-transcriptional level. However, our group has recently shown that hPTMs are abundant and varied in Trypanosoma cruzi, the etiological agent of Chagas Disease, signaling for possible conserved epigenetic functions. Here, we applied an optimized mass spectrometry-based proteomic workflow to provide a high-confidence comprehensive map of hPTMs, distributed in all canonical, variant and linker histones of T. cruzi. Our work expands the number of known T. cruzi hPTMs by almost 2-fold, representing the largest dataset of hPTMs available to any trypanosomatid to date, and can be used as a basis for functional studies on the dynamic regulation of chromatin by epigenetic mechanisms and the selection of candidates for the development of epigenetic drugs against trypanosomatids.
在人类和其他真核生物中,组蛋白翻译后修饰(hPTMs)在基因表达的表观遗传调控中起着至关重要的作用。相反,在动基体生物寄生虫中,基因调控主要发生在转录后水平。然而,我们的研究小组最近表明,在恰加斯病的病原体克氏锥虫中,hPTMs 丰富多样,可能具有保守的表观遗传功能。在这里,我们应用了一种经过优化的基于质谱的蛋白质组学工作流程,提供了一个高可信度的 hPTMs 全图谱,分布在 T. cruzi 的所有经典、变体和连接组蛋白中。我们的工作将已知的 T. cruzi hPTMs 数量增加了近两倍,这是迄今为止任何动基体生物中 hPTMs 的最大数据集,可作为研究表观遗传机制对染色质动态调控以及选择针对动基体生物的表观遗传药物候选物的功能研究的基础。